With the advantages of high-resolution and viewing of live organisms, optical microscopy has become an important tool for biological research and continues to open new avenues in its capabilities. In recent years, image resolution and speed has been dramatically improved. However, the improvement of the resolution and penetration depth for optical microscopy is still in its infancy. As light passes through biological tissue, it can be absorbed, refracted and scattered, limiting the resolution and depth of optical imaging in biological tissues. Overcoming these challenges will benefit a wide range of applications from basic biological research to clinical investigations. The present invention addresses these challenges.